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Course Availability

This course is only available to trainees days after purchase.
It would need to be repurchased by the trainee if not completed in the allotted time period.
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Description

The notion that the immune system can recognize and eliminate tumor cells was recognized in the late 19th century with the observation that cancer patients who developed infections occasionally experienced disease regression. Initial approaches to stimulate anti-tumor immunity such as Coley’s toxins were relatively crude and largely unrewarding. Over the past 100 years various attempts to improve cancer therapy by stimulating the immune system provided only incremental improvements in outcome with benefit to small numbers of patients affected by a narrow spectrum of disease (e.g., melanoma, renal cell carcinoma). More recently, significant advancements in molecular techniques and genetically engineered mouse models have generated a comprehensive understanding regarding the role of peripheral tolerance and subsequent immune-editing in the failure of the immune system to recognize and eliminate tumor cells. Specifically, the roles of various immune cell subsets such as regulatory T cells, myeloid derived suppressor cells, and M2 macrophages in suppressing anti-tumor responses have been well characterized, providing opportunities for therapeutic intervention. Integral to this has been the discovery of key immune regulators termed inhibitory checkpoint molecules including CTLA-4 and PD1 resulting in the development of antibody based approaches to block signaling of these critical proteins. The first half of the review session will focus on understanding the mechanisms that permit tumor cells to evade immune destruction. The second half of the review will describe how the use of checkpoint inhibitors has transformed the treatment of many cancers in human medicine. Lastly, recent successes combining checkpoint inhibitors with both standard treatment modalities (radiation, chemotherapy) and small molecule inhibitors will be briefly discussed.

Objectives

Learning Objectives:

• Understand the various components of the innate and immune systems and the mechanisms that drive central and peripheral tolerance.
• Understand the factors that drive immunoediting and immune suppression in the setting of cancer.
• Be familiar with various treatment strategies aimed at resotring anti-tumor immune responses, particularly those involving checkpoint inhibitors.